Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372730 | Bioorganic & Medicinal Chemistry Letters | 2009 | 9 Pages |
Abstract
A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C12 (PO)/EC50 ratios.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Frank Ruebsam, Douglas E. Murphy, Chinh V. Tran, Lian-Sheng Li, Jingjing Zhao, Peter S. Dragovich, Helen M. McGuire, Alan X. Xiang, Zhongxiang Sun, Benjamin K. Ayida, Julie K. Blazel, Sun Hee Kim, Yuefen Zhou, Qing Han, Charles R. Kissinger,